Download Cholinergics Chart

Cholinergics
Drug
Characteristics
AGONISTS
▫Acetylcholine (ACh)
▫Pilocarpine
natural, tertiary, M
▫Cevimeline (Exovac)
M
▫Methacholine
synthetic, quaternary, M in
heart
synthetic, quaternary, M & N
synthetic, quaternary, M in GI
& UT
natural, lipid soluble tertiary,
N
▫Carbamylcholine (Carbachol)
▫Bethanechol (Urecholine)
▫Nicotine
REVERSIBLE CHOLINESTERASE INHIBITORS
▫Physostigmine (Antilirium)
natural, tertiary, M & N
▫Neostigmine (Prostigmin)
Uses/Mechanism
direct intracoronary injection to dx. vasospastic angina pectoris
-topical miotic for glaucoma
-tx. drymouth in cancer or Sjogren’s synd. (autoimmune salivary dysfxn)
tx. for drymouth
-old tx for tachycardias
-aerosol to dx. bronchial hyperreactivity
topical miotic agent
-tx. stasis conditions of bladder or GI, esp. post-partum and after
general anesthesia
-leads to conversion from activation to depolarizing blockade
-tx. for nicotine withdrawal sx.
-maybe good for cognition in Alzheimer’s, ↓Parkinson’s
BEWARE acute poisoning = ANS stim, CNS excitation, convulsions,
depression, sk. m. paralysis
topical miotic for glaucoma
synthetic, quaternary, N
Notes
met. by CYP2D6 and 3A3/4=
maybe toxic w/ ketoconazole etc
not met. by cholinesterases =
longer duration than ACh
not met. by AChE
-not. met by cholinesterases
-don’t give if GI obstruction (P)
-crosses placenta, sec. in milk
-widely dist. in CNS
-highly addictive
met. by plasma ester hydrolysis
-can cause seizures
-oral abs. 15X less than parenteral
met. by plasma ester hydrolysis
-Anticholinesterase AND agonist action = tx myasthenia gravis
-motility of GI or UT
-reverses sk. m. blockade by competitive antagonist (d-tubocurarine)
▫Pyridostigmine (Mestinon)
same as neo, but longer duration = most common oral tx for myasthenia
▫Edrophonium (Tensilon)
synthetic, quaternary
-Anticholinesterase AND agonist action at motor endplate = systemic
only lasts 5 min
action is almost totally on sk. m. = diagnostic for myasthenia
▫Tacrine (Cognex)
not used much anymore
-tx. cognitive sx. of Alzheimer’s (but not dementia)
-crosses BBB, hepatotoxic
▫Donepezil (Aricept)
piperidine-based
-tx. cognitive sx. of Alzheimer’s w/ long duration = once daily dose
met. by CYP2D6 and 3A3/4
milder side effects, no hepatotoxicity
▫Rivastigmine (Exelon)
carbamate structure
Alzheimer’s tx that is met. slower, also inhibits pseudoChE
good if poor response to donepezil
▫Galantamine (Reminyl)
tertiary alkaloid
Alzheimer’s Tx
IRREVERSIBLE CHOLINESTERASE INHIBITORS (ORGANOPHOSPHATES)
▫Echothiophate
very polar, exc. in urine, lipid
topical miotic agent for eye (effects last 3 days)
soluble, so can be abs. thru
▫malathion
common home and garden insecticide, controls lice topically
can be met. by mammals
skin
▫Parathion
must first be conv. in liver to active form, paraoxon; only for pros
is NOT met. by mammals
▫Sarin
“nerve gas” for war, terrorism
MUSCARINIC ANTAGONISTS
▫Atropine
natural alkaloid
tx for motor symptoms of Parkinson’s
“atropine flush” @ toxic levels
-can block vagal afferents to heart = tachycardia = tx. for sinus
-mainly met. in liver, some exc.
bradycardia after MI
unchanged in urine
-↓motility in GI, threshold volume for sensory micturation reflex
-sustained cyclopegia and mydriasis topically on eye
▫Scopolamine
100X more potent than atropine in ascending reticular core =produces somnolence and hypnosis with amnesia
may produce delerium and hallucinations
-anti motion sickness (abs. thru skin well enough to give as patch)
▫Tolterodine (Detrol)
tertiary
tx. for urinary urgency
met. by liver
▫Oxybutinin (Ditropan)
tertiary
tx. for post-operative bladder spasm, also tx for urinary urgency
met. by liver, available as patch
▫Tropicamide (Mydriacyl)
tertiary
short-duration mydriatic/cycloplegic topical on eye
▫Ipratropium (Atrovent)
quaternary
tx. as aerosol for COPD, asthma, etc…
▫Propantheline
quaternary
spasmolytic for GI tract, tx. for GI hypermotility
▫Benztropine (Cogentin)
tertiary
-tx parkinson’s motor sx.
▫Pirenzepine
tertiary, M1
under investigation for peptic ulcer. No heart side effects
NICOTINIC COMPETITIVE ANTAGONISTS
▫d-tubocurarine
natural alkaloid
-↓BP initially due to: 1. ANS ganglia block, 2. Histamine from Masts
t0.5=3.8hr, ½ met., ½ exc kidney
▫vecuronium (Norcuron)
synthetic, steroid-based
slight ganglionic blockade can reduce GI tract motility, very popular
biliary excretion
no histamine release
▫atracurium (Tracrium)
synthetic
only a little Histamine release, intermediate duration of action
inactivated by spont. breakdown.
landanoside, a breakdown. product, may excite the CNS
since unstable at plasma pH = safe
for renal and hepatic failure
▫doxacurium (Nuromax)
specific for neuromuscular jxn = few side effects, no Hist., long action
exc. by kidney
▫mivacurium (Mivacron)
shortest duration, slow onset, only a little Histamine release
met. by pseudoChE’s in plasma
DEPOLARIZING BLOCKERS
▫Succinylcholine (Anectine)
synthetic
rapid onset, 5 min duration; significant hyperkalemia
pseudoChE met. to succinic acid
best for relaxing laryngeal mm. to insert an airway
and choline
GANGLIONIC BLOCKADE AGENTS
▫Trimethaphan (Arfonad)
blocks early EPSP and thus ganglionic transmission
tx. HTN emergencies, or create hypotension for brain surgery
▫Hexamethonium
quaternary amine
possible HTN drug
not really used anymore
▫Mecamylamine (Inversine)
secondary amine
possible use for nicotine-sensitive CNS disorders like Tourette’s
ACh RELEASE BLOCKERS
▫Botulinum Toxin A (Botox)
local injection to tx strabismus, torticollis, wrinkles, possibly migranes
MISCELANEOUS SKELETAL MUSCLE RELAXANTS (ARE NOT CHOLINERGIC)
▫Pralidoxime
▫Dantrolene (Dantrium)
blocks Ca from sarcoplasmic reticulum. Used only for spasticity tx. in
pts w/ upper motor neuron lesions, malignant hyperthermia